The specific aim of this study is to develop detail methodology and valid criteria for the evaluation of the biologic properties of endodontic materials. This would give manufacturers and involved authorities a tool to spot and exclude toxic and inferior materials. The long-term goal is directed towards the development of biocompatible endodontic filling materials, and the protection of the patient against inferior and unsafe materials. In the final analysis, the project is designed to establish a possible correlation between simple and inexpensive laboratory tests, e.g., tissue culture tests or implantation tests in soft tissue or bone, and the expensive usage tests. This could serve as a basis for the evaluation of biocompatibility according to the Medical Device Bill of 1976. The magnitude of the socio-economic health related problems is that 17,390,000 endodontic treatments were carried out in one year (ADA Survey, 1979). Assuming an optimistic 9-10% average failure rate and $300.00 per treatment, the cost in cash is 1/2 billion dollars, excluding lost time to patient and society. A material, which is introduced into connective tissue, will cause tissue destruction, inflammation, and foreign body reaction dependent upon level of toxicity. Thus, as it is important to characterize the material by its irritant properties, it is equally important to develop methods to prevent its extrusion into the periapical tissue e.g., the dentin chip method. The plan is to prepare and examine the tissue now embedded in paraffin blocks derived from the former grant period, and to perform implant tests with selected materials with updated methodology. The materials are: gutta percha points in combination with the sealers - Kloroperka N.O., Kerr, AH26 - and dentin chips as a barrier between the irritant sealers and the adjacent tissue; the biologically active collagen gel, compared to Ca(OH)2 U.S.P., which the former aspires to replace; N2, and Hydron as examples of intended permanent paste fillings. Select materials from this group will be used in the upgraded subcutaneous and intraosseous implant experimentations, morphometric methods will be used for the histologic evaluation, and statistical methods used to correlate the implant tests to the usage test, with the final goal of substituting the implant tests for the expensive usage tests.